Computer Simulations Show That Liquid–Liquid Phase Separation Enhances Self-Assembly

Biomolecular condensates are liquid- or gel-like droplets
of proteins
and nucleic acids formed at least in part through liquid–liquid
phase separation. Condensates enable diverse functions of cells and
the pathogens that infect them, including self-assembly reactions.
For example, it has been shown that many viruses form condensates
within their host cells to compartmentalize capsid assembly and packaging
of the viral genome. Yet, the physical principles controlling condensate-mediated
self-assembly remain incompletely understood. In this article, we
use coarse-grained molecular dynamics simulations to study the effect
of a condensate on the assembly of icosahedral capsids. The capsid
subunits are represented by simple shape-based models to enable simulating
a wide range of length and time scales, while the condensate is modeled
implicitly to study the effects of phase separation independent of
the molecular details of biomolecular condensates. Our results show
that condensates can significantly enhance assembly rates, yields,
and robustness to parameter variations, consistent with previous theoretical
predictions. However, extending beyond those predictions, the computational
models also show that excluded volume enables control over the number
of capsids that assemble within condensates. Moreover, long-lived
aberrant off-pathway assembly intermediates can suppress yields within
condensates. In addition to elucidating condensate-mediated assembly
of viruses and other biological structures, these results may guide
the use of condensates as a generic route to enhance and control self-assembly
in human-engineered systems.